A review of recent advances in electrochemical and photoelectrochemical late-stage functionalization classified by anodic oxidation, cathodic reduction, and paired electrolysis

• Nian Li,
• Ruzal Sitdikov,
• Ajit Prabhakar Kale,
• Joost Steverlynck,
• Bo Li and
• Magnus Rueping

Beilstein J. Org. Chem. 2024, 20, 2500–2566, doi:10.3762/bjoc.20.214

• anodic oxidation cleaves the diazene, resulting in the formation of an acyl radical and the release of molecular nitrogen. The subsequent step involves the decarboxylation of the acyl radical to produce an alkyl radical. This method was successfully applied to the late-stage functionalization of

Natural resorcylic lactones derived from alternariol

• Joachim Podlech

Beilstein J. Org. Chem. 2024, 20, 2171–2207, doi:10.3762/bjoc.20.187

• , respectively) [243], showed inhibitory potential against various protein kinases with IC50 values of 1.5–9.7 µg/mL [147], and displayed significant scavenging activities against nitrite [243]. Biosynthetic decarboxylation of desmethylaltenusin affords biaryl 49, which was isolated from Penicillium sp. [244

• ] and from Talaromyces sp. [243]. It showed significant α-glucosidase inhibition with an IC50 value of 2.2 μM [244] and was a potent scavenger of DPPH and of nitrite [243]. Decarboxyaltenusin (50) was reported in 1974 to be obtained by chemical decarboxylation of altenusin (47) and by reduction of

Multicomponent syntheses of pyrazoles via (3 + 2)-cyclocondensation and (3 + 2)-cycloaddition key steps

• Ignaz Betcke,
• Alissa C. Götzinger,
• Maryna M. Kornet and
• Thomas J. J. Müller

Beilstein J. Org. Chem. 2024, 20, 2024–2077, doi:10.3762/bjoc.20.178

Harnessing the versatility of hydrazones through electrosynthetic oxidative transformations

• Aurélie Claraz

Beilstein J. Org. Chem. 2024, 20, 1988–2004, doi:10.3762/bjoc.20.175

• produced hydrazones 29. After deprotonation, the authors proposed that the carboxylate anion underwent SET anodic oxidation/decarboxylation/radical cyclization sequence to form radical intermediates 34. Subsequent second anodic oxidation and deprotonation yielded the desired heteroaromatic 5-membered rings

• 38. As such, the iodide electrolyte served as an electromediator to both promote the decarboxylation process and protect the aniline product from overoxidation. Importantly, a control experiment without electricity but in the presence of molecular iodine instead proceeded smoothly, thereby confirming

Negishi-coupling-enabled synthesis of α-heteroaryl-α-amino acid building blocks for DNA-encoded chemical library applications

• Matteo Gasparetto,
• Balázs Fődi and
• Gellért Sipos

Beilstein J. Org. Chem. 2024, 20, 1922–1932, doi:10.3762/bjoc.20.168

• protocols [70][71]. In these experiments, compounds 6b and 6i proved to be unstable under on-DNA conditions as they failed to form esters 8b and 8i. Closely related structures, such as α-aminobenzothiazol-2-ylacetic acid is known to undergo decarboxylation at room temperature [72]. Compound 8t underwent

• decarboxylation during the hydrolysis step. Compounds 6j, 6l and 6r passed validation in moderate to good yields (Scheme 8). Conclusion In conclusion, by taking advantage of the recent advances in the Negishi cross-coupling reaction we obtained a broad range of heteroarylacetates starting from heteroaromatic

Access to 2-oxoazetidine-3-carboxylic acid derivatives via thermal microwave-assisted Wolff rearrangement of 3-diazotetramic acids in the presence of nucleophiles

• Ivan Lyutin,
• Vasilisa Krivovicheva,
• Grigory Kantin and
• Dmitry Dar’in

Beilstein J. Org. Chem. 2024, 20, 1894–1899, doi:10.3762/bjoc.20.164

• -methoxyethylamine. Attempts to obtain directly 2-oxoazetidine carboxylic acid (or its decarboxylation product) or its trifluoroethyl ester by running the synthesis with water or trifluoroethanol were also unsuccessful. Acylation of the π-excessive double bonds of N-alkylindole and dihydropyran by the in situ

• high yields of the target compounds. When stored individually or in solution at room temperature, the acids 4 gradually decompose and undergo decarboxylation and other accompanying processes. The example of acid 4a demonstrates the possibility of easy amidation to form new β-lactam derivatives 3s and

2-Heteroarylethylamines in medicinal chemistry: a review of 2-phenethylamine satellite chemical space

• Carlos Nieto,
• Alejandro Manchado,
• Ángel García-González,
• David Díez and
• Narciso M. Garrido

Beilstein J. Org. Chem. 2024, 20, 1880–1893, doi:10.3762/bjoc.20.163

• -heteroarylethylamine chemical space is constituted by the biogenic amine histamine (43). In a similar fashion as dopamine and epinephrine produced from ʟ-phenylalanine along the catecholamine pathway, histamine is generated from the amino acid ʟ-histidine (42) via enzymatic decarboxylation promoted by ʟ-histidine

Syntheses and medicinal chemistry of spiro heterocyclic steroids

• Laura L. Romero-Hernández,
• Ana Isabel Ahuja-Casarín,
• Penélope Merino-Montiel,
• Sara Montiel-Smith,
• José Luis Vega-Báez and
• Jesús Sandoval-Ramírez

Beilstein J. Org. Chem. 2024, 20, 1713–1745, doi:10.3762/bjoc.20.152

• decarboxylation of the carboxylic residue when heated at reflux of methanol. After the regioselective cycloadditions, spiro compounds 49a,b were obtained in yields ranging from 75% to 91% (Scheme 15). Related derivatives have similarly been achieved in good to excellent yields [32][33]. Recently, López et al

Chemo-enzymatic total synthesis: current approaches toward the integration of chemical and enzymatic transformations

• Ryo Tanifuji and
• Hiroki Oguri

Beilstein J. Org. Chem. 2024, 20, 1693–1712, doi:10.3762/bjoc.20.151

• TylGI loads a methylmalonyl-CoA onto the acyl carrier protein (ACP) in module 1. The ketosynthase-like decarboxylase (KSQ) domain catalyzes the decarboxylation of the loaded methylmalonyl moiety, and subsequent modules 2 and 3 extend the carbon chain using two molecules of malonyl-CoA. The β

Mining raw plant transcriptomic data for new cyclopeptide alkaloids

• Draco Kriger,
• Michael A. Pasquale,
• Brigitte G. Ampolini and
• Jonathan R. Chekan

Beilstein J. Org. Chem. 2024, 20, 1548–1559, doi:10.3762/bjoc.20.138

• lack an oxidative decarboxylation of the C-terminus (Figure 3, arabipeptin A). Our transcriptome mining results further support the prevalence of cyclopeptide alkaloids in the Rubiaceae family. Chiococca alba (Snowberry), Cinchona calisaya (Yellow Cinchona), Gardenia jasminoides (Cape Jasmine), C

Benzylic C(sp³)–H fluorination

• Alexander P. Atkins,
• Alice C. Dean and
• Alastair J. J. Lennox

Beilstein J. Org. Chem. 2024, 20, 1527–1547, doi:10.3762/bjoc.20.137

• benzylic fluorination method that employed unprotected amino acids as radical precursors, Figure 12 [50]. Oxidation of glycine by Ag(II) promotes decarboxylation and results in the α-amino radical, which performs a HAT on the benzylic substrate to furnish the benzylic radical. This subsequently undergoes

• facilitating HAT to produce a benzylic radical. Fluorine-atom-transfer (FAT) with Selectfluor then gave the benzyl fluoride. The low acidity of phenylacetic acids in polar aprotic solvents disfavoured decarboxylation (via an SET pathway) promoting HAT from the benzylic position. By using a mixture of 1:1 MeCN

• /H2O and heating, the decarboxylation pathway could be enabled to afford primary benzyl fluorides. In the same year, Barham and co-workers also showed that the radical dication TEDA2+• was capable of HAT on unactivated C(sp3)–H, enabling fluorination at these positions [63]. This work utilised para

Tetrabutylammonium iodide-catalyzed oxidative α-azidation of β-ketocarbonyl compounds using sodium azide

• Christopher Mairhofer,
• David Naderer and
• Mario Waser

Beilstein J. Org. Chem. 2024, 20, 1510–1517, doi:10.3762/bjoc.20.135

• decomposition and also some decarboxylation during column chromatography or upon prolonged reaction times. Also, tests with analogous β-ketoketones and β-ketoamides (compare with azidation products 5 and 6, Scheme 3) did not give any products but resulted in the formation of a variety of unidentified side

Electrophotochemical metal-catalyzed synthesis of alkylnitriles from simple aliphatic carboxylic acids

• Yukang Wang,
• Yan Yao and
• Niankai Fu

Beilstein J. Org. Chem. 2024, 20, 1497–1503, doi:10.3762/bjoc.20.133

• synthesis; electrophotocatalysis; radical decarboxylation; Introduction Alkylnitriles and their derivatives are widely found in pharmaceuticals and biologically active compounds [1][2][3]. In addition, within the field of synthetic organic chemistry, nitriles are synthetically useful handles that can be

• electrophotochemical transition metal catalysis [26][27][28][29][30][31] as a unique and powerful synthetic platform for radical decarboxylative functionalization of aliphatic carboxylic acids [32][33][34][35][36][37]. In particular, the commonly required high activation energy for radical decarboxylation was provided

• decarboxylative cyanation of arylacetic acids [35][36][37]. Considering the widespread availability of aliphatic carboxylic acids and the significant synthetic and medicinal importance of alkylnitriles, we envisioned that the electrophotochemical Ce-catalyzed radical decarboxylation of alkyl carboxylic acids in

Generation of alkyl and acyl radicals by visible-light photoredox catalysis: direct activation of C–O bonds in organic transformations

• Mithu Roy,
• Bitan Sardar,
• Itu Mallick and
• Dipankar Srimani

Beilstein J. Org. Chem. 2024, 20, 1348–1375, doi:10.3762/bjoc.20.119

• recent photocatalysis methodologies in the field of C–O bond activation. As conventional techniques, such as Barton decarboxylation, create hazardous wastes, the use of alternative feedstocks, including alcohols and acids, has been encouraged to achieve sustainability. The recent advancements not only

Cofactor-independent C–C bond cleavage reactions catalyzed by the AlpJ family of oxygenases in atypical angucycline biosynthesis

• Jinmin Gao,
• Liyuan Li,
• Shijie Shen,
• Guomin Ai,
• Bin Wang,
• Fang Guo,
• Tongjian Yang,
• Hui Han,
• Zhengren Xu,
• Guohui Pan and
• Keqiang Fan

Beilstein J. Org. Chem. 2024, 20, 1198–1206, doi:10.3762/bjoc.20.102

• aldehyde–acid intermediate 11. In JadG-catalyzed reactions, compound 11 participated in a reaction with ʟ-isoleucine to yield 6. In contrast, in AlpJ- or Flu17-catalyzed reactions, 11 underwent decarboxylation and an aldol reaction, giving rise to intermediate 12. Subsequent dehydration of 12 led to the

Bismuth(III) triflate: an economical and environmentally friendly catalyst for the Nazarov reaction

• Manoel T. Rodrigues Jr.,
• Aline S. B. de Oliveira,
• Ralph C. Gomes,
• Amanda Soares Hirata,
• Lucas A. Zeoly,
• Hugo Santos,
• João Arantes,
• Catarina Sofia Mateus Reis-Silva,
• João Agostinho Machado-Neto,
• Leticia Veras Costa-Lotufo and
• Fernando Coelho

Beilstein J. Org. Chem. 2024, 20, 1167–1178, doi:10.3762/bjoc.20.99

• optimized conditions for substrates 9dc,dl, we found that in addition to the products of interest, they also formed the decarboxylated products as inseparable mixtures. Given this result, we investigated milder conditions to avoid decarboxylation. In doing so, we reacted the substrate 9dc for 24 h at room

• temperature. Despite this long reaction time, we still observed formation of the decarboxylated derivative, and we could also partly recover the starting material (Table 2). Decarboxylation reactions of indanones have previously been described in the literature. In 2008, Itoh et al. investigated the Nazarov

• decarboxylated product 14. In 2010, Zhang et al. [76] developed a methodology catalyzed by In(OTf)3 for the synthesis of bicycles, and they also verified that decarboxylation occurred when the reaction remained at 80 °C for 6 h (Scheme 1). The same behavior was observed by France during the synthesis of the

(Bio)isosteres of ortho- and meta-substituted benzenes

• H. Erik Diepers and
• Johannes C. L. Walker

Beilstein J. Org. Chem. 2024, 20, 859–890, doi:10.3762/bjoc.20.78

• decarboxylation then yields 1,2-cubane 88. This synthesis reduced the number of synthetic steps from eight, in the previously known patented synthesis from 2007 [54], to four. MacMillan and co-workers also developed a number of decarboxylative cross-coupling reactions to allow access to an even wider range of 1,2

• ), deprotection, decarboxylation, oxidation, nitrogen extrusion (to cyclobutadiene) and Diels–Alder reaction yielded annulated tricycle 164. Further intramolecular [2 + 2] cycloaddition formed cubane precursor 165. From diketone 165, 1,3-cubane 166 was obtained by Favorskii ring contraction followed by

Chemical and biosynthetic potential of Penicillium shentong XL-F41

• Ran Zou,
• Xin Li,
• Xiaochen Chen,
• Yue-Wei Guo and
• Baofu Xu

Beilstein J. Org. Chem. 2024, 20, 597–606, doi:10.3762/bjoc.20.52

• pathway (Figure 5). Briefly, the prenyl group is attached to tryptophan through a prenylation reaction catalyzed by ShnA, followed by the decarboxylation of the carboxy group by ShnC. Subsequently, compound 2 is formed by the addition of succinimide to N15 in 1 via a reaction catalyzed by ShnB. The

Recent developments in the engineered biosynthesis of fungal meroterpenoids

• Zhiyang Quan and
• Takayoshi Awakawa

Beilstein J. Org. Chem. 2024, 20, 578–588, doi:10.3762/bjoc.20.50

• the αKG-dependent dioxygenase have been analyzed in detail due to its relatively small molecular weight and the low costs of its cofactors: αKG, ascorbic acid, and iron ions. The αKG reacts with iron and molecular oxygen to form the highly reactive Fe(IV)=O via oxidative decarboxylation. This active

Mechanisms for radical reactions initiating from N-hydroxyphthalimide esters

• Carlos R. Azpilcueta-Nicolas and
• Jean-Philip Lumb

Beilstein J. Org. Chem. 2024, 20, 346–378, doi:10.3762/bjoc.20.35

• [25][26] (Scheme 1) and have found applications in a number of functional group interconversions mediated by radical chain decarboxylation [27]. However, their widespread use in synthesis, especially in complex molecular settings, suffers from significant disadvantages. These include thermal and

• (PC•–) (Scheme 4A). This strong reducing agent mediates the one-electron reduction of the NHPI ester 10, forming radical anion intermediate 11. Fragmentation of 11 via N–O bond homolysis and decarboxylation forms the key tertiary radical 12 with concomitant formation of phthalimidyl anion (–Nphth) and

• irradiation, EDA complex 74 triggered a radical chain process initiated by B–B bond cleavage, forming boryl-NHPI ester radical 75 and boryl radical 76. Subsequent decarboxylation of 75 yields carbon-centered radical 9 and boryl-phthalimide byproduct 77. Meanwhile DMA-ligated B2cat2 78 is formed upon

Synthesis of π-conjugated polycyclic compounds by late-stage extrusion of chalcogen fragments

• Aissam Okba,
• Pablo Simón Marqués,
• Kyohei Matsuo,
• Naoki Aratani,
• Hiroko Yamada,
• Gwénaël Rapenne and
• Claire Kammerer

Beilstein J. Org. Chem. 2024, 20, 287–305, doi:10.3762/bjoc.20.30

• bronze in refluxing quinoline, thus triggering a S-extrusion along with a decarboxylation reaction (Scheme 3) [56]. From a retrosynthetic point of view, this example nicely illustrates the fact that polyannelated thiepines, and more generally S-, Se- and Te-based heteropines, are straightforward

• chemically-induced S-extrusion (and concomitant decarboxylation) from a dibenzothiepine precursor [56]. Top: Conversion of dinaphthothiepine bisimides 3a,b and their sulfoxide analogues 4a,b into PBIs 6a,b by S-extrusion triggered by electron injection, photo- and thermal activation. Bottom

Beyond n-dopants for organic semiconductors: use of bibenzo[d]imidazoles in UV-promoted dehalogenation reactions of organic halides

• Kan Tang,
• Megan R. Brown,
• Chad Risko,
• Melissa K. Gish,
• Garry Rumbles,
• Phuc H. Pham,
• Oana R. Luca,
• Stephen Barlow and
• Seth R. Marder

Beilstein J. Org. Chem. 2023, 19, 1912–1922, doi:10.3762/bjoc.19.142

• concert with sacrificial weak reductants (Figure 1b) [8][9][10][11]. Another approach is to add ambient-stable precursors to reaction mixtures: for example, reducing Wanzlick dimers and related species (Figure 1a, ii) have been formed from precursors through in situ decarboxylation [12] or deprotonation

Anion–π catalysis on carbon allotropes

• M. Ángeles Gutiérrez López,
• Mei-Ling Tan,
• Giacomo Renno,
• Augustina Jozeliūnaitė,
• J. Jonathan Nué-Martinez,
• Javier Lopez-Andarias,
• Naomi Sakai and
• Stefan Matile

Beilstein J. Org. Chem. 2023, 19, 1881–1894, doi:10.3762/bjoc.19.140

• forward. Decarboxylation of the resulting intermediate IV then affords the chiral addition product 6. This enolate addition is in kinetic competition with simple decarboxylation, yielding thioacetate 7. Under most conditions, this decarboxylation is favored. Anion–π catalysis selectively accelerates the

• intrinsically disfavored but significant enolate addition by stabilizing the planar sp2 intermediate II that has to add before decarboxylation can occur [2][61]. The non-planar sp3 keto intermediate I that can decarboxylate through intermediate V without preceding enolate addition is less stabilized on the

• planar π surfaces of anion–π catalysts. The A/D product ratio is thus a convenient measure for anion–π catalysis, the larger the better, with A/D > 1, the intrinsic selectivity for decarboxylation has been inverted [2][3][18]. Applying lessons from simpler anion–π catalysts, trialkylamines were tethered

Recent advancements in iodide/phosphine-mediated photoredox radical reactions

• Tinglan Liu,
• Yu Zhou,
• Junhong Tang and
• Chengming Wang

Beilstein J. Org. Chem. 2023, 19, 1785–1803, doi:10.3762/bjoc.19.131

• smoothly delivered an electron donor–acceptor (EDA) complex II via coulombic interactions. Upon 456 nm blue LED light irradiation, the EDA complex II underwent a single electron transfer (SET) process, followed by subsequent decarboxylation to produce the alkyl radical intermediate A, accompanied by

• facilitated by the process of photoexcited radical decarboxylation. On the other hand, the copper catalytic cycle involved the capture of alkyl radicals by the copper complex B, the activation of heteroatom-containing substrates 30 by a base-mediated proton transfer, and the subsequent reductive elimination

•  15) [27]. This method involved a series of steps, including the formation of an EDA complex, decarboxylation, radical addition, C–H functionalization, and annulation. Various primary, secondary, and tertiary alkyl N-hydroxyphthalimide esters 33 showed potential as viable substrates for the synthesis

Decarboxylative 1,3-dipolar cycloaddition of amino acids for the synthesis of heterocyclic compounds

• Xiaofeng Zhang,
• Xiaoming Ma and
• Wei Zhang

Beilstein J. Org. Chem. 2023, 19, 1677–1693, doi:10.3762/bjoc.19.123

• -type AMYs in multicomponent, one-pot, and stepwise reactions for the synthesis of diverse heterocycles related to some bioactive compounds and natural products. Keywords: [3 + 2] cycloaddition; decarboxylation; 1,3-dipolar; double cycloaddition; one-pot synthesis; multicomponent reaction; semi

• aldehydes and α-amino esters (via dehydration) or α-amino acids (via decarboxylation) could be classified based on the substitution groups on the N atom to: 1) N-substituted (N–R type), 2) hydrogen containing (N–H type), and 3) metal complexes (N–M type) (Figure 1) [16][17]. These AMYs could also be